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Laboratory for Chemical Synthesis and Catalysis

Contract number
14.A12.31.0005
Time span of the project
2013-2015

As of 30.01.2020

10
Number of staff members
15
scientific publications
1
Objects of intellectual property
General information

Name of the project: Applications of biorthogonal chemistry in research of living systems

Strategy for Scientific and Technological Development Priority Level: в, г


Goals and objectives

Research directions: Membrane receptors, new topical antifungal medications for preventing and treatment of dermatomycoses in extreme environmental conditions, new antimicrobe medications with system action for therapy of resistive forms that do not react to treatment, new anti-tumor medications with low general toxicity, new means of protection of plants for agriculture, antimicrobial agents based on polyphenols and polymetoxybenzone of plant nature.

Project objective: Producing new fundamental scientific knowledge on structural and functional features of membrane receptors, determining key segments to which ligands and potential medications that impact them directly link, as well as determining molecular mechanisms of functioning of these receptors.


The practical value of the study

  • We have produced new geroprotectors – substances capable of increasing lifespans of animals.
  • With have synthesized macrocyclic substances with antibacterial properties.
  • Our researchers have investigated a click reaction (i.e. the reaction that easily flows even in biological environments of organisms) that leads to formation of new links between various molecules and that is catalyzed by biological objects, in particular, bu the adenosine receptor.
  • We have tested a number of substances synthesized at the Laboratory for their antifungal activity. The research has shown that criteria of sensibility to the Candida parapsilosis strain ATCC 22019 meet the requirements of GOST R ISO 16256-2015 and «A. fumigatus ATCC 46645 Clinical and Laboratory Standards Institute document M38-A2». Howevr, the clinical isolates of Microsporum canis VGNKI 19, Trichophyton rubrum VGNKI 2002 are resistive to fluconazole, but show activity towards ketoconazole. Comparative evaluation of the activity and the spectrum of active in vitro with respect to fungal strains including dermatophytes for new synthesized substances and agents for comparison of fluconazole and ketoconazole has shown that compounds showing activity with respect to Candida parapsilosis comparable to fluconazole are the most promising. Unlike fluconazole, new substances suppress growth of filamentous fungi.

Implemented results of research: Results of our research can be used for synthesis of new antibiotics, antifungal and other types of medications, producing biologically active supplements for extending lifespan.

Education and career development:

  • Two candidate dissertations have been defended
  • Four educational courses have been developed: «Synthesis of specialized heterocyclic compounds», «Cell-to-cell signaling systems», «Medical chemistry», «Basics of medical chemistry».
  • Four members of the academic staff have been admitted to the postgraduate school. 
  • We have organized career enhancement and occupational retraining. Four people have completed training at the courses.

Organizational and structural changes: The Laboratory is part of the Living Systems Center of the Moscow Institute of Physics and Technology. Molecules synthesized by the academic staff of the Laboratory that have been selected by medical chemists and bioinformaticians are now undergoing tests in bioscreening laboratories, development of innovative medications and laboratory pre-clinical tests at the Living Systems Center of the Moscow Institute of Physics and Technology.

Collaborations:

  • Moscow State University (Russia), Institute of Bioorganic Chemistry of the Russian Academy of Sciences named after academicians M. M. Shemyakin and Yu. A. Ovchinnikov (Russia), University of Southern California (USA), Scripps Research Institute (USA): joint research and publications

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Ivanenkov Y.A., Vasilevski S.V., Beloglazkina E.K., Vanzcool A.S. et al.
Design, Synthesis and Biological Evaluation of Novel Potent MDM2/p53 Small-Molecule Inhibitors. Bioorganic & Medicinal Chemistry Letters 25(2): 404–409 (2015).
Ivanenkov Y.A.,Veselov M.S., Shakhbazyan A.G. et al.
A Comprehensive Insight into the Chemical Space and ADME Features of Small Molecule NS5A Inhibitors. Current Topics in Medicinal Chemistry 16(12): 1372–1382 (2016).
Ivanenkov Y.A., Veselov M.S., Aladinskiy V.A. et al.
In Silico Approaches to the Design of NS5A Inhibitors. Current Topics in Medicinal Chemistry 16(12): 1383–1391 (2016).
Ivanenkov Y.A., Veselov M.S., Chufarova N.V. et al.
Non-dopamine Receptor Ligands for the Treatment of Parkinson's Disease. Insight into the related chemical/property space. Molecular Diversity 20(1): 345–365 (2016).
Shadrin I.A., Rzhevskii S.A., Rybakov V.B., Babaev E.V.
Sonogashira Reaction of the Indolizine Ring. Synthesis 47(19): 2961–2964 (2015).
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